BACKGROUND: In this paper, we explore the concept of multi-objective optimization in the field of metabolic engineering when both continuous and integer decision variables are involved in the model. In particular, we propose a multi-objective model that may be used to suggest reaction deletions that maximize and/or minimize several functions simultaneously. The applications may include, among others, the concurrent maximization of a bioproduct and of biomass, or maximization of a bioproduct while minimizing the formation of a given by-product, two common requirements in microbial metabolic engineering. RESULTS: Production of ethanol by the widely used cell factory Saccharomyces cerevisiae was adopted as a case study to demonstrate the usefulness of the proposed approach in identifying genetic manipulations that improve productivity and yield of this economically highly relevant bioproduct. We did an in vivo validation and we could show that some of the predicted deletions exhibit increased ethanol levels in comparison with the wild-type strain. CONCLUSIONS: The multi-objective programming framework we developed, called MOMO, is open-source and uses POLYSCIP (Available at http://polyscip.zib.de/). as underlying multi-objective solver. MOMO is available at http://momo-sysbio.gforge.inria.fr.

As client demands grow, optical network operators are required to introduce lightpaths of higher line rates in order to groom more demand into their network capacity. For a given fiber network and a given set of client demands, the minimum cost network design is the task of assigning routing paths and wavelengths for a minimum cost set of lightpaths able to groom all client demands. The variant of the optical network design problem addressed in this paper considers a transparent optical network, single hop grooming, client demands of a single interface type, and lightpaths of two line rates. We discuss two slightly different mixed integer linear programming models that define the network design problem combining grooming, routing, and wavelength assignment. Then, we propose a parameters increase rule and three types of additional constraints that, when applied to the previous models, make their linear relaxation solutions closer to the integer solutions. Finally, we use the resulting models to derive a hybrid heuristic method, which combines a relax-and-fix approach with an integer linear programming-based local search approach. We present the computational results showing that the proposed heuristic method is able to find solutions with cost values very close to the optimal ones for a real nation-wide network and considering a realistic fiber link capacity of 80 wavelengths. Moreover, when compared with other approaches used in the problem variants close to the one addressed here, our heuristic is shown to compute solutions, on average, with better cost values and/or in shorter runtimes.